Glaucoma is a progressive disease which leads to optic nerve damage, and, ultimately, total loss of vision. The causes of this disease have been the subject of extensive studies for many years, but are still not fully understood. The principal symptom of and/or risk factor for the disease is elevated intraocular pressure or ocular hypertension due to excess aqueous humor in the anterior chamber of the eye. The causes of aqueous humor accumulation in the anterior chamber are not fully understood. It is known that elevated intraocular pressure can be at least partially controlled by administering drugs which reduce either the production of aqueous humor within the eye, such as beta-blockers and carbonic anhydrase inhibitors, or increase the flow of aqueous humor out of the eye, such as miotics and sympathomimetics. Latanoprost, a novel prostaglandin F2α analogue, is a selective prostanoid FP receptor agonist which reduces the intraocular pressure by increasing the outflow of aqueous humor.
The relationship between EP receptor activation and intraocular pressure lowering effects is well known. There are currently four recognized subtypes of the EP receptor: EP1, EP2, EP3, and EP4 (J. Lipid Mediators Cell Signaling, volume 14, pages 83-87 (1996)). Intraocular pressure may be lowered by ligands capable of EP2 receptor activation, such as PGE2 and certain of its synthetic analogs (Journal of Ocular Pharmacology, volume 4, number 1, pages 13-18 (1988); Journal of Ocular Pharmacology and Therapeutics, volume 11, number 3, pages 447-454 (1995)).
Numerous publications have suggested the use of prostaglandin agonists for treating bone disorders and/or glaucoma, including: U.S. Pat. No. 4,599,353, U.S. Pat. No. 5,296,504, WO 1998/028264, U.S. Pat. No. 6,288,120, U.S. Pat. No. 6,492,412, U.S. Pat. No. 6,649,657, JP 2000053566, EP 1 000 619, U.S. Pat. No. 6,344,485, EP 1 205 189, US 2002/0115695, US 2002/0161026, US 2004/0176423, WO 2003/045371, US 2003/0166631, WO 1999/019300, U.S. Pat. No. 6,498,172, JP 20011163779, EP 1 108 426, US 2005/203086 and WO 2004/078169, the disclosures of each are hereby incorporated by reference in their entirety for all purposes. There remains, however, a continuing need in this field of art for alternative therapies for the treatment of glaucoma.